|
ADs | Wnt signaling | Key signaling molecule | Models | Evaluated factor(s) | Effect/mechanism | Reference(s) |
|
RA | Canonical pathway | SFRP4 | Rat RA model | MeCP2 | Downregulating β-catenin by activating SFRP4 in RA rats | [34] |
GSK3β | MSCs | TNF-α | Ameliorating inflammatory responses | [43] |
DKK1 | MSCs | NF-κB | Suppressing Wnt signaling by upregulating DKK1; inhibiting inflammatory responses, and promoting bone resorption and formation | [44, 45] |
Wnt1, TCF/LEF1, SPRP1 | FLS | proMMP3; fibronectin | An enhanced Wnt signaling promotes RA progression | [18] |
Wnt1; WISP3 | FLS; synovial tissue | Inflammatory cytokines | High levels of Wnt1, Fzds, and WISP3 in RA tissues | [46] |
PKC mediated noncanonical pathway | Wnt5a/Fzd5 | FLS | IL6; IL15; RANKL; NF-κB | Contributing to the activated state of FLS in RA | [47] |
Wnt signaling | Wnt7b | Cartilage, bone, and synovium in RA and OA samples | TNF-α IL-1b; IL-6 | Evidence of an involvement of Wnt signaling in the pathobiology of both RA and OA | [48] |
Wnt10b | Mouse | CD28 T cells | Inhibition of CD28 costimulation by CTLA-4Ig promotes T cell Wnt10b production and bone formation | [49] |
|
AS | Wnt signaling | DKK1 | Jurkat T cells | TNF-α | Downregulating Wnt signaling by increasing DDK1 expression and ameliorating inflammatory responses | [50] |
Wnt signaling | Chondrocytes | Induces differentiation of mesenchymal cells into osteoblast lineages | Active Wnt signaling contributes to osteophyte formation and joint remodeling | [7] |
Noncanonical pathway | Wnt5a, Wnt10b | MSCs | TNF-α | TNF-α induced Wnt5a and Wnt10b may be involved in the effects of inflammation on bone formation | [51] |
|
SSc |
Wnt signaling | Wnt2, Wnt3a, Wnt5a, Wnt10b, DDK2, LEF-1, WIF-1, β-catenin | Skin biopsies and peripheral blood samples from SSc patients and mouse model | TGF-β; IL4; IL13; IL17; IL33; IFN; IL13 | An enhanced Wnt signaling promotes disease progression | [19, 52, 53] |
Wnt1, Wnt10b and DKK1 | B cells, mouse model | IL6 | The activation of Wnt signaling or inhibition of DKK1 induces severe fibrosis and lipoatrophy in animal models | [54] |
WIF-1, β-catenin | Fibroblasts from SSc | ATF3; HDAC3 | An oxidative DNA damage induced by SSc autoreactive antibodies enables Wnt activation that contributes to fibrosis | [55] |
|
AA | Canonical pathway | GSK3β, Wnt10b | NK cells | IFN-γ | A decreased Wnt signaling impairs anagen initiation and the ability of stem cells to drive differentiation of hair keratinocytes | [56] |
Wnt signaling | β-catenin, Wnt7a | C3H/HeJ mouse model of AA | Wnt signaling | Vitamin A enhances Wnt signaling to activate hair follicle SCs | [57] |
|
CCL | Noncanonical pathway | Wnt5a, ROR1 | HEK293 cells, leukemia B-1 cells | NF-κB | ROR1 promotes CLL cells to receive survival signals
| [58] |
Canonical pathway | Wnt/β-catenin | Leukemia B-1 cells, MEC-1 cells, CCL clinical samples | IL-6, inflammatory factors | Quercetin or metadherin inhibits leukemia cell expansion by blocking Wnt/β-catenin pathway and diminishes production of inflammatory factors in ADs and neoplasia | [59–61] |
|
CIA | Wnt signaling | Fzd2 | PGRN-deficient Tregs | TNF-α | Wnt signaling contributes to the PGRN regulation of Tregs | [62] |
|
EAU | Canonical pathway | DKK3, SFRP2 | RGM | IL17 | Wnt inhibitors DKK3 and SFRP2 are downregulated in EAU; an enhanced Wnt signaling is involved in ERU pathogenesis | [6, 63] |
|
IBD |
Canonical pathway | TCF4 | CD patients | Polymorphism analysis | Correlation of a functional variant TCF6 with early onset ileal CD | [64] |
TCF1, LRP6 | Paneth cells | Alpha-defensins HD-5 and HD-6 | A TCF-1-mediated Wnt signaling may contribute to the barrier dysfunction in CD | [65] |
LRP6 | CD patients | Polymorphism analysis | Correlation of a functional variant LRP6 with early onset ileal CD | [33] |
|
JRA | Canonical pathway | Wnt3a, WISP3, TCF1 | SFMCs, Treg cells | FOXP3 |
A dysregulated Wnt signaling in the synovium inhibits Treg cell function and promotes JIA pathogenesis | [42] |
|
MS | Wnt signaling | Wnt3a, Wnt5a, ROR2, β-catenin | EAE mice | Mechanical hyperalgesia and allodynia of paws in EAE mice | An aberrant activation of Wnt signaling contributes to the development of EAE-related chronic pain | [12] |
|
Psoriasis | Canonical pathway | Activates Wnt signaling by LiCl | Manic-depressive patients | Thyroid microsomal antibodies | LiCl induced thyroid dysfunction and abrogated Treg cells suppressive capacity | [66] |
Wnt signaling | Wnt5a, Fzd2, Fzd5, DKKs, WIF-1 | Biopsies of psoriasis patients | IL-1α, TNF-α, IFN-γ, TGF-α | Canonical Wnt signaling toward noncanonical pathways driven by interactions between Wnt5a and its cognate receptors in psoriasis, accompanied by impaired homeostatic inhibition of Wnt signaling by WIF-1 and dickkopf | [67] |
|
SLE | Canonical pathway | DKK1 | BM-MSCs | TNF-α | Wnt signaling plays a critical role in the senescence of SLE BM-MSCs through the p53/p21 pathway | [68] |
|
T1DM | Canonical pathway | GSK3β | INS-1E rat insulinoma cells, rat islets | Cell proliferation and survival | An enhanced Wnt signaling by inhibiting CSK3 promotes β-cell proliferation | [69, 70] |
|
UIP | Noncanonical pathway | Wnt5a | Primary fibroblasts of lung tissues with UIP | Fibronectin, α5-integrin, β-catenin | Wnt5a promotes fibroblast proliferation in IPF and UIP | [71] |
|